The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis

Yoshiki Morita, Atsushi Nomura, Yukio Yuzawa, Kazuhiro Nishikawa, Nigishi Hotta, Fujio Shimizu, Seiichi Matsuo

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Persistent proteinuria and tubulointerstitial lesions are important signs of progressive renal disease. The purpose of this study was to assess the role of complement in the development of tubulointerstitial lesions in rats with proteinuria due to primary glomerulonephritis. Mesangial proliferative glomerulonephritis was induced in mononephrectomized rats by intravenous injection of monoclonal antibody (mAb) 1-22-3 (Clin Exp Immunol 102: 181-185, 1995). As early as 24 h after the injection, proteinuria became evident, persisted throughout the observation period, and was associated with mesangial cell proliferation and tubulointerstitial lesions when examined at 7 and 14 d after mAb administration. Deposition of rat C3 and C5b-9 was observed at the luminal surface of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complement by injections of cobra venom factor starting at day 3 developed glomerulonephritis and proteinuria comparable to rats of group I, but complement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group III were injected with mAb and, from day 3, with soluble complement receptor type 1, which became detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and the severity of tubulointerstitial lesions was reduced compared with rats in group I. These results indicate that, in this model of primary mesangial proliferative glomerulonephritis with proteinuria, the development of tubulointerstitial lesions is associated with activation of serum complement at the level of tubular brush border, and tubulointerstitial lesions can be reduced by inhibition of complement activity.

Original languageEnglish
Pages (from-to)1363-1372
Number of pages10
JournalJournal of the American Society of Nephrology
Volume8
Issue number9
Publication statusPublished - 01-09-1997

Fingerprint

Glomerulonephritis
Proteinuria
Monoclonal Antibodies
Complement Membrane Attack Complex
Complement Receptors
Complement C3
Injections
Mesangial Cells
Complement Activation
Microvilli
Intravenous Injections
Cell Proliferation
Observation
Urine
Kidney
Serum

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Morita, Yoshiki ; Nomura, Atsushi ; Yuzawa, Yukio ; Nishikawa, Kazuhiro ; Hotta, Nigishi ; Shimizu, Fujio ; Matsuo, Seiichi. / The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis. In: Journal of the American Society of Nephrology. 1997 ; Vol. 8, No. 9. pp. 1363-1372.
@article{ce425c159d3a423e9e947704db1437da,
title = "The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis",
abstract = "Persistent proteinuria and tubulointerstitial lesions are important signs of progressive renal disease. The purpose of this study was to assess the role of complement in the development of tubulointerstitial lesions in rats with proteinuria due to primary glomerulonephritis. Mesangial proliferative glomerulonephritis was induced in mononephrectomized rats by intravenous injection of monoclonal antibody (mAb) 1-22-3 (Clin Exp Immunol 102: 181-185, 1995). As early as 24 h after the injection, proteinuria became evident, persisted throughout the observation period, and was associated with mesangial cell proliferation and tubulointerstitial lesions when examined at 7 and 14 d after mAb administration. Deposition of rat C3 and C5b-9 was observed at the luminal surface of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complement by injections of cobra venom factor starting at day 3 developed glomerulonephritis and proteinuria comparable to rats of group I, but complement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group III were injected with mAb and, from day 3, with soluble complement receptor type 1, which became detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and the severity of tubulointerstitial lesions was reduced compared with rats in group I. These results indicate that, in this model of primary mesangial proliferative glomerulonephritis with proteinuria, the development of tubulointerstitial lesions is associated with activation of serum complement at the level of tubular brush border, and tubulointerstitial lesions can be reduced by inhibition of complement activity.",
author = "Yoshiki Morita and Atsushi Nomura and Yukio Yuzawa and Kazuhiro Nishikawa and Nigishi Hotta and Fujio Shimizu and Seiichi Matsuo",
year = "1997",
month = "9",
day = "1",
language = "English",
volume = "8",
pages = "1363--1372",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "9",

}

The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis. / Morita, Yoshiki; Nomura, Atsushi; Yuzawa, Yukio; Nishikawa, Kazuhiro; Hotta, Nigishi; Shimizu, Fujio; Matsuo, Seiichi.

In: Journal of the American Society of Nephrology, Vol. 8, No. 9, 01.09.1997, p. 1363-1372.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis

AU - Morita, Yoshiki

AU - Nomura, Atsushi

AU - Yuzawa, Yukio

AU - Nishikawa, Kazuhiro

AU - Hotta, Nigishi

AU - Shimizu, Fujio

AU - Matsuo, Seiichi

PY - 1997/9/1

Y1 - 1997/9/1

N2 - Persistent proteinuria and tubulointerstitial lesions are important signs of progressive renal disease. The purpose of this study was to assess the role of complement in the development of tubulointerstitial lesions in rats with proteinuria due to primary glomerulonephritis. Mesangial proliferative glomerulonephritis was induced in mononephrectomized rats by intravenous injection of monoclonal antibody (mAb) 1-22-3 (Clin Exp Immunol 102: 181-185, 1995). As early as 24 h after the injection, proteinuria became evident, persisted throughout the observation period, and was associated with mesangial cell proliferation and tubulointerstitial lesions when examined at 7 and 14 d after mAb administration. Deposition of rat C3 and C5b-9 was observed at the luminal surface of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complement by injections of cobra venom factor starting at day 3 developed glomerulonephritis and proteinuria comparable to rats of group I, but complement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group III were injected with mAb and, from day 3, with soluble complement receptor type 1, which became detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and the severity of tubulointerstitial lesions was reduced compared with rats in group I. These results indicate that, in this model of primary mesangial proliferative glomerulonephritis with proteinuria, the development of tubulointerstitial lesions is associated with activation of serum complement at the level of tubular brush border, and tubulointerstitial lesions can be reduced by inhibition of complement activity.

AB - Persistent proteinuria and tubulointerstitial lesions are important signs of progressive renal disease. The purpose of this study was to assess the role of complement in the development of tubulointerstitial lesions in rats with proteinuria due to primary glomerulonephritis. Mesangial proliferative glomerulonephritis was induced in mononephrectomized rats by intravenous injection of monoclonal antibody (mAb) 1-22-3 (Clin Exp Immunol 102: 181-185, 1995). As early as 24 h after the injection, proteinuria became evident, persisted throughout the observation period, and was associated with mesangial cell proliferation and tubulointerstitial lesions when examined at 7 and 14 d after mAb administration. Deposition of rat C3 and C5b-9 was observed at the luminal surface of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complement by injections of cobra venom factor starting at day 3 developed glomerulonephritis and proteinuria comparable to rats of group I, but complement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group III were injected with mAb and, from day 3, with soluble complement receptor type 1, which became detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and the severity of tubulointerstitial lesions was reduced compared with rats in group I. These results indicate that, in this model of primary mesangial proliferative glomerulonephritis with proteinuria, the development of tubulointerstitial lesions is associated with activation of serum complement at the level of tubular brush border, and tubulointerstitial lesions can be reduced by inhibition of complement activity.

UR - http://www.scopus.com/inward/record.url?scp=0030727779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030727779&partnerID=8YFLogxK

M3 - Article

C2 - 9294827

AN - SCOPUS:0030727779

VL - 8

SP - 1363

EP - 1372

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 9

ER -